Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction
Autor: | Siti Balkis Budin, Norsyahida Mohd Fauzi, Rebecca H. Ritchie, Satirah Zainalabidin, Anand Ramalingam |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cardiac function curve Mitochondrial ROS Nicotine Science Cardiology Myocardial Reperfusion Injury Inflammation Pharmacology Resveratrol medicine.disease_cause Article Antioxidants Mitochondria Heart Ventricular Dysfunction Left 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Myocytes Cardiac chemistry.chemical_classification Reactive oxygen species Multidisciplinary Ventricular Remodeling biology Drug discovery business.industry Atrial Remodeling Rats Disease Models Animal Oxidative Stress 030104 developmental biology chemistry Sirtuin biology.protein Medicine medicine.symptom Reactive Oxygen Species business 030217 neurology & neurosurgery Oxidative stress medicine.drug |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague–Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia–reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia–reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction. |
Databáze: | OpenAIRE |
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